Blockade of angiotensin II receptors inhibits the increase in blood pressure induced by insulin.
To elucidate whether hyperinsulinemia increases blood pressure by increasing sympathetic outflow via the activation of the central angiotensin system, insulin was infused into urethane-anesthetized rats intravenously (i.v.) or intracerebroventricularly (i.c.v.) under euglycemic conditions. Infusion (i.v.) of insulin elicited pressor effects in a dose-dependent manner (13, 20, and 40 mU/min). Although depressor responses to i.v. injections of hexamethonium were significantly greater in insulin-infused than in saline-infused rats, i.v. captopril and d(CH2)5Tyr(Me)-arginine vasopressin did not show any differences between the groups. Infusions (i.c.v.) of insulin (8 mU/10 microl) also induced cardiovascular acceleration and augmented the depressor response to i.v. hexamethonium in insulin-infused rats. The i.c.v. pretreatment with the angiotensin II antagonist losartan inhibited the pressor responses to both the i.c.v. and i.v. infusion of insulin. These results suggest that the increase in blood pressure induced by euglycemic hyperinsulinemia is elicited by sympathetic activation and that hyperinsulinemia stimulates the angiotensin system in the brain to increase sympathetic nerve activity.
Nakata
T
T
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Takeda
K
K
Hatta
T
T
Kiyama
M
M
Moriguchi
J
J
Miki
S
S
Kawa
T
T
Morimoto
S
S
Nakamura
K
K
Uchida
A
A
Itoh
H
H
Sasaki
S
S
Nakagawa
M
M
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D018738:Hexamethonium / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D007328:Insulin / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013566:Sympathomimetics / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D005730:Ganglionic Blockers; D006727:Hormone Antagonists; D007328:Insulin; D013566:Sympathomimetics; D000804:Angiotensin II; D001127:Arginine Vasopressin; D018738:Hexamethonium; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D002216:Captopril; D019808:Losartan; D009638:Norepinephrine